14-3-3β and γ differentially regulate peroxisome proliferator activated receptor γ<inf>2</inf> transactivation and hepatic lipid metabolism

Sodam Park, Seungmin Yoo, Jeonghan Kim, Hyoung Tae An, Minsoo Kang, Je Sang Ko

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Peroxisome proliferator activated receptor (PPAR) γ<inf>2</inf> plays important roles in glucose and lipid metabolism in hepatocytes. PPARγ<inf>2</inf> is involved in metabolic disorders, including obesity, diabetes, and fatty liver disease. Although the 14-3-3 proteins participate in a variety of cell signal pathways, the roles of the 14-3-3 proteins in regulating PPARγ<inf>2</inf> transactivation and hepatic lipid metabolism are unknown. We identified 14-3-3β and γ as PPARγ<inf>2</inf> transcriptional regulators. We found that 14-3-3β and γ competitively interacted with the phosphorylated Ser273 of PPARγ<inf>2</inf>, which is important for regulating glucose and lipid metabolism. 14-3-3β increased the transcriptional activity of PPARγ<inf>2</inf> and enhanced the expression levels of PPARγ<inf>2</inf> target genes involved in lipogenesis and lipid transport. In contrast, 14-3-3γ decreased PPARγ<inf>2</inf> transactivation and reduced the expression levels of PPARγ<inf>2</inf> target genes. A high concentration of free fatty acids increased PPARγ<inf>2</inf> expression and lipid accumulation. 14-3-3β enhanced hepatic lipogenesis, which is a major symptom of non-alcoholic fatty liver disease. However, 14-3-3γ suppressed hepatic lipid accumulation in the presence of high free fatty acids. These findings indicate that 14-3-3β and γ are novel PPARγ<inf>2</inf> regulators and are involved in hepatic lipid metabolism. 14-3-3β and γ can be therapeutic target molecules to treat non-alcoholic fatty liver disease.

Original languageEnglish
Article number918
Pages (from-to)1237-1247
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1849
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

Keywords

  • 14-3-3 proteins
  • Fatty liver disease
  • Lipogenesis
  • PPARγ<inf>2</inf>

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Molecular Biology
  • Structural Biology

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